Ehrengruber Markus U, Lundstrom Kenneth
Kantonsschule Hohe Promenade, Zurich, Switzerland.
Curr Protoc Neurosci. 2007 Oct;Chapter 4:Unit 4.22. doi: 10.1002/0471142301.ns0422s41.
Alphaviral vectors based on Semliki Forest virus and Sindbis virus infect many host cell types, causing rapid and high-level transgene expression. Compared to other viruses used to infect CNS cell and tissue preparations, Semliki Forest virus and Sindbis virus exhibit an outstanding preference for neurons rather than glial cells. High-titer vector generation typically requires biosafety level 1 or 2 containment and occurs in less than 2 days. Wild-type vectors are cytotoxic, permitting short-term transgene expression. However, mutant vectors with decreased cytotoxicity, to prolong host cell survival, have been developed. They also increase transgene expression and cellular coinfection, permitting heteromeric protein expression in individual cells. Other mutants with temperature-dependent control of transgene expression and altered host cell preference to target interneurons and astrocytes rather than principal neurons are available. Because of these advantages, alphaviral vectors are increasingly used in neurobiological and other studies, including structural biology, vaccine development, and cancer treatment.
基于辛德毕斯病毒和Semliki森林病毒的甲病毒载体可感染多种宿主细胞类型，能实现快速且高水平的转基因表达。与用于感染中枢神经系统细胞和组织制剂的其他病毒相比，Semliki森林病毒和辛德毕斯病毒对神经元的偏好明显高于神经胶质细胞。高滴度载体的产生通常需要生物安全1级或2级防护，且在不到2天的时间内即可完成。野生型载体具有细胞毒性，只能实现短期转基因表达。不过，为延长宿主细胞存活时间，已开发出细胞毒性降低的突变载体。它们还能增加转基因表达和细胞共感染，从而在单个细胞中实现异源蛋白表达。此外，还有其他一些突变体，它们对转基因表达具有温度依赖性控制，并且改变了宿主细胞偏好，以靶向中间神经元和星形胶质细胞而非主要神经元。由于这些优势，甲病毒载体在神经生物学及其他研究中越来越常用，包括结构生物学、疫苗开发和癌症治疗等领域。
